The CURE: Digestive Diseases Research Core Center (CURE: DDRCC) is composed of a cohesive group of physicians and basic scientists with strong independent peer-reviewed grant-supported research programs in the biology of the gut, with special emphasis upon regulation of mucosal cell function, gut neuroscience and signal transduction mechanisms. CURE, created in 1974, has grown and evolved into a broadly based gastrointestinal research organization with multiple affiliations, principally the VA and UCLA. Since 1989, a fundamental component of CURE has been the NIDDKsupported CURE: DDRCC. The research emphasis of the Center is acquisition of new knowledge about molecular, cellular and physiological processes that control gastrointestinal function and translation of this knowledge into development of therapy for patients with gastrointestinal diseases. The research programs of the CURE: DDRCC members can be broadly divided into four major areas: (1) gastroduodenal mucosal physiology and disease;(2) intestinal and pancreatic physiology and disease;(3) neural regulation of gastroenteric function and neuroenteric disease;and (4) mechanism of action of gastrointestinal peptides, including receptor regulation, signal transduction and control of cell proliferation. The Biomedical Research Cores outlined in this proposal provide ready access to technologies, and to clinical and biological materials that are essential to the programs of center members. These Cores provide access to modem cellular imaging to study signaling proteins and their functions, animal models for studying physiology and pathophysiology, and access to a broad range of techniques and patients for clinical studies. New services incorporated in this proposal include proteomics, GI cell biology, functional genomics, signal transduction and development of gene transfer vectors. The Administrative Core provides a wide range of administrative support for members and for center activities including a dynamic enrichment program. The Pilot and Feasibility and the Named New Investigator Programs have provided successful mechanisms for aiding the development of new research programs in gastrointestinal biology by young investigators. The center provides an optimal environment for cooperation and collaboration among its investigators, who have had a major impact on digestive disease research over the past three decades and promise to have an even larger impact upon expanded research areas with continued support from the Center.